Aluminum is one of the most widely used nonferrous metals and an important industrial material, especially for automotive coatings. However, potential toxicity caused by aluminum in humans limits the used of this metal. α-alumina is the most stable form of aluminum in various phases. Although the results of studies evaluating the dermal toxicity of α-alumina remained unclear, this compound can still be used as a pigment in cosmetics for humans. In the current study, we further evaluated the dermal cytotoxic effects of α-alumina on human skin cells and an in vivo mouse model. We also measured the in vitro penetration profile of flake-like α-alumina in porcine skin and assessed the degree of cellular metabolic disorders. Our findings demonstrated that treatment with flake-like α-alumina did not significantly affect cell viability up to 24 h. This compound was found to have a non-penetration profile based on a Franz modified diffusion cell assay. In addition, flake-like α-alumina was not found to induce dermal inflammation as assessed by histology of epidermal architecture, hyperplasia, and the expression of Interleukin-1β and Cyclooxygenase-2. Results of the cellular metabolic disorder assay indicated that flake-like α-alumina does not exert a direct effect on human skin cells. Taken together, our findings provided not only evidence that flake-like α-alumina may serve as a pearlescent pigment in cosmetics but also experimental basis utilizing α-alumina for human application. Our results also obviously provide new insight of the further toxicity study to aluminum based nanoparticles for skin.